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. 2023 Aug 23;13(1):13805.
doi: 10.1038/s41598-023-40879-y.

miRNA profiling as a complementary diagnostic tool for amyotrophic lateral sclerosis

Jack Cheng #  1   2 , Wen-Kuang Ho #  1 , Bor-Tsang Wu  3 , Hsin-Ping Liu  4 , Wei-Yong Lin  5   6
Affiliations

miRNA profiling as a complementary diagnostic tool for amyotrophic lateral sclerosis

Jack Cheng et al. Sci Rep. .

Abstract

Amyotrophic lateral sclerosis (ALS), the most prevalent motor neuron disease characterized by its complex genetic structure, lacks a single diagnostic test capable of providing a conclusive diagnosis. In order to demonstrate the potential for genetic diagnosis and shed light on the pathogenic role of miRNAs in ALS, we developed an ALS diagnostic rule by training the model using 80% of a miRNA profiling dataset consisting of 253 ALS samples and 103 control samples. Subsequently, we validated the diagnostic rule using the remaining 20% of unseen samples. The diagnostic rule we developed includes miR-205-5p, miR-206, miR-376a-5p, miR-412-5p, miR-3927-3p, miR-4701-3p, miR-6763-5p, and miR-6801-3p. Remarkably, the rule achieved an 82% true positive rate and a 73% true negative rate when predicting the unseen samples. Furthermore, the identified miRNAs target 21 genes in the PI3K-Akt pathway and 27 genes in the ALS pathway, including notable genes such as BCL2, NEFH, and OPTN. We propose that miRNA profiling may serve as a complementary diagnostic tool to supplement the clinical presentation and aid in the early recognition of ALS.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
The workflow of this study.
Figure 2
Figure 2
The predictive model generated by machine learning and its performance. (A) The rule model judging where a sample is ALS or control, where “1” denotes ALS and “0” denotes control. The value in the conditional expression is the batch-corrected count of the miRNA. (B) The ROC curve of the rule model, with AUC of 0.831.
Figure 3
Figure 3
The miRNA expression fold change of the miRNAs identified by the rule model. Error bars stand for the standard error of the mean (SEM); while *, **, and *** stand for p-value < 0.05, 0.01, and 0.001 of Student’s T-test, respectively. The upper right panel shows the number of experimentally validated mRNA targets of miRNA, with the full list provided in the corresponding supplementary files.
Figure 4
Figure 4
The protein interaction network of the mRNA targets of the identified miRNAs. Red balls indicate proteins in the Amyotrophic lateral sclerosis of KEGG, while blue balls indicate proteins in the PI3K-Akt signaling pathway of KEGG.
Figure 5
Figure 5
The Venn diagram showing that the miRNA-target sets are nearly mutually exclusive. (A) The ALS genes. (B) The PI3K-Akt genes.
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